Trazodone

Serotonin antagonist and reuptake inhibitor (SARI), Antidepressant, Sleep aid

Trazodone

Desyrel (original IR), Oleptro (ER), Trittico

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Titration strategies

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Summary

Classes

Serotonin antagonist and reuptake inhibitor (SARI), Antidepressant, Sleep aid

Common uses

Major depressive disorder (FDA, original indication)▲0▼, Insomnia (off-label; vastly more common in current practice than the depression indication)▲0▼, Anxiety disorder adjunct (off-label)▲0▼, PTSD-related sleep disturbance (off-label)▲0▼

Pharmacy

Starting dose

Insomnia (off-label): 25-50 mg PO at bedtime, titrate to effect. Depression: 150 mg/day divided BID-TID; titrate to 400 mg/day outpatient or 600 mg/day inpatient

Preparations

IR tablets 50, 100, 150, 300 mg; Oleptro ER tablets 150, 300 mg

US FDA Max

400 mg/day outpatient; 600 mg/day inpatient

Pharmacology

Routes

Oral

Onset

Sleep effect within 30-60 minutes; antidepressant effect over 1-2 weeks

Duration

~6-8 hours (IR); 24 hours (Oleptro ER)

Half-life

Biphasic: ~3-6 hours alpha, ~5-9 hours beta

Bioavailability

~65% (oral)

Pregnancy

Limited human data; observational signals inconclusive.^{[citation needed]}

Legal status

Rx-only in US. Carries the antidepressant Boxed Warning for suicidality in children, adolescents, and young adults

Purported mechanism

Combined strong 5-HT2A antagonism with weaker serotonin reuptake inhibition (the SARI class signature). At the low doses used for insomnia (25-100 mg), 5-HT2A antagonism, H1 antihistaminergic effect, and α1-adrenergic antagonism dominate, producing sedation; at antidepressant doses (≥150 mg) the SRI contribution adds. The active metabolite mCPP is a 5-HT2C agonist that may contribute to anxiogenesis in some patients.▲0▼ Priapism is a recognized rare adverse effect via α1 antagonism in penile vasculature and is the marquee counseling point for male patients.